He was the husband of the Brigantian queen Cartimandua, who handed Caratacus over to the Romans after he sought sanctuary with her in AD 51. The Brigantes were at this time an independent kingdom, but, in the words of the Roman historian Tacitus, "loyal to Rome and defended by our arms". When Cartimandua subsequently divorced him in favour of his armour-bearer, Vellocatus, Venutius took took up arms against her, and soon took Caratacus's place as the foremost leader of British resistance to the Romans. During the governorship of Aulus Didius Gallus (52-57) he raised an army and invaded the Brigantian kingdom, but after some heavy fighting was defeated by a legion under the command of Caesius Nasica.
In 69 troops were withdrawn from Britain to fight in the civil wars in Rome that followed the death of Nero, and weak governors could not control dissention among the army. Taking advantage of this instability, Venutius staged a second insurrection against Cartimandua, who appealed for Roman assistance. She was evacuated by auxiliary troops, but Venutius was left in control of the kingdom.
Venutius's eventual defeat is not recorded. Vespasian's legate Quintus Petilius Cerialis (governor 71-74) campaigned in Brigantian territory, with some success, although how much is unclear. The Brigantes were not completely subdued for some time: the Roman poet Juvenal and the Greek geographer Pausanias refer to warfare against the Brigantes in the early 2nd century.